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Bio-Thera Solutions Announces Initiation of Pivotal Phase III Study of BAT8001 for Patients with Metastatic Breast Cancer

On November 1, 2018 Bio-Thera Solutions, reported the initiation of a Phase III clinical trial evaluating the efficacy and safety of its investigational HER2 Antibody-Drug Conjugate (ADC), BAT8001, in patients with HER-2 positive metastatic breast cancer who previously received trastuzumab separately or in combination with taxanes (Press release, BioThera Solutions, NOV 1, 2018, View Source [SID1234530650]). The trial is designed to compare BAT8001 versus lapatinib combined with capecitabine which is 2nd-line standard of care for metastatic breast cancer patients in China.

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"Metastatic breast cancer is a difficult to treat cancer that impacts hundreds of thousands of patients around the world. Patients with metastatic breast cancer need more treatment options that provide an improved survival benefit," said Shengfeng Li, CEO of Bio-Thera Solutions. "This Phase III trial is an important step in the development of BAT8001, potentially providing patients with metastatic breast cancer a new treatment option."

This Phase III, multicenter, randomized, open-label, controlled trial will recruit approximately 410 patients in China. The primary efficacy outcome of the trial is progression-free survival (PFS). Other pre-specified outcome measures include overall survival (OS), and objective response rate (ORR). The safety and immunogenicity of BAT8001 will also be evaluated in the trial.

More information on the trial is available at View Source
(CTR20180157).

About BAT8001

BAT8001 is an investigational HER2-ADC being evaluated in multiple tumor types. HER2 is a naturally occurring receptor that is overexpressed in many types of cancer, including breast cancer and gastric cancer. BAT8001 is being developed for use as a single agent and in combination with other agents for the treatment of multiple cancers. The BAT8001 clinical study program will be expanded beyond metastatic cancer to other HER2-positive cancers, including gastric cancer, over the next 12 months.

About Antibody-Drug Conjugates

Antibody-drug Conjugates or ADCs are designed to harness the targeting ability of monoclonal antibodies (mAbs) to deliver cytotoxic agents selectively to tumor cells by linking the monoclonal antibody and cytotoxic agent through a chemical linker. An ideal ADC consists of: 1) a highly selective mAb for a tumor-associated antigen that has little or no expression on normal cells, 2) a potent cytotoxic agent designed to induce target cell death after being internalized in the tumor cell and released and 3) a chemical linker that is stable in circulation but releases the cytotoxic agent in target cells. By selectively delivering a cytotoxic agent directly inside a tumor cell, ADCs increase the safety and tolerability of the cytotoxic agent relative to giving the cytotoxic agent systemically to the patient.

About Metastatic Breast Cancer

Metastatic breast cancer is not a specific type of breast cancer, it is breast cancer that has spread beyond the breast to other organs in the body. Metastatic breast cancer is most often found in the bones, lungs, liver or brain but can be found in other locations in the body. Although metastatic breast cancer has spread to another part of the body, it is still considered and treated as breast cancer. Typically, metastatic breast cancer arises months or years after a person has completed treatment for early or locally advanced breast cancer. This is sometimes called a distant recurrence. Some patients are first diagnosed with metastatic breast cancer. This is called de novo metastatic breast cancer. The risk of metastasis after breast cancer treatment varies from person to person and depends greatly on the biology of the tumor, the stage at the time of the original diagnosis and the treatments for the original cancer.

Alliance for Cancer Gene Therapy Announces Kevin Honeycutt as CEO and President

On November 1, 2018 Alliance for Cancer Gene Therapy (ACGT), the nation’s only public charity exclusively funding cancer cell and gene therapy research, reported that Kevin Honeycutt will be joining ACGT as its new CEO and President, effective December 3, 2018 (Press release, Alliance Pharma, NOV 1, 2018, View Source [SID1234530649]). Mr. Honeycutt was most recently the President and CEO of the Avon Breast Cancer Crusade (ABCC) since 2015. At ACGT, his principal role will be to enhance the vision of ACGT, begun in 2001 by its co-founders, Barbara Netter and her late husband Edward, to spearhead ACGT’s current focus on funding the next generation of challenges brought by metastatic cancers and solid tumors, and to continue to build our alliances and joint ventures.

Mrs. Netter stated that, "We are delighted to have Kevin as ACGT’s new CEO and President at this momentous time in the field of cancer cell and gene therapy. His experience at ABCC, in which he led several highly successful fundraising campaigns, positions him to hit the ground running to oversee ACGT‘s fundraising and grants program. Kevin brings a depth of knowledge and experience in the oncology space and strategic thinking which perfectly fits within the ACGT model."

Mr. Honeycutt said that, "ACGT’s outstanding Board of Directors and pre-eminent Scientific Advisory Council, together with the leadership of Barbara Netter, the ACGT staff, and ACGT’s current and past grant recipients, were key to my enthusiasm in joining ACGT. Given the remarkable advances being made in the field of cancer cell and gene therapy, it is an opportune time to be working in cancer research with significant opportunities to advance the understanding of how to treat the disease and give patients the best chances for successful long-term favorable outcomes."

Prior to his years at ABCC, Mr. Honeycutt served as Executive Director of the Avon Foundation for Women for five years, and in cause marketing. He previously led projects for, among others, the American Diabetes Association, DaVita, Inc. / The Kidney Trust, the Entertainment Industry Foundation and the Jane Goodall Institute

F-star to Disclose Targets and Preclinical Data on New Agonist Bispecific Antibody Programmes

On November 1, 2018 F-star, a clinical-stage biopharmaceutical company pioneering the development of novel bispecific antibodies that target the immune system to fight cancer, reported that it will present preclinical data on two new proprietary bispecific antibodies at the SITC (Free SITC Whitepaper) Annual Meeting, PEGS Summit Europe and the ESMO (Free ESMO Whitepaper) Immuno-Oncology Congress (Press release, f-star, NOV 1, 2018, View Source [SID1234530648]).

Checkpoint antagonists dominate the clinical landscape and yet despite encouraging progress, only a small patient population reaches a durable and clinically meaningful response. Current approaches have shown limited efficacy for poorly immunogenic tumours which harness different and often multiple escape or resistance mechanisms to attenuate the local immune response.

FS120 is a dual agonist mAb² simultaneously targeting OX40 (CD134, TNFRSF4) and CD137 (4-1BB). FS222 is an agonist/antagonist mAb² against CD137 and PD-L1 (Programmed Death-Ligand 1). Both OX40 and CD137 are co-stimulatory molecules, part of the Tumour Necrosis Factor Receptor Super Family (TNFRSF). Unlike checkpoint antagonists, engagement of OX40 or CD137 on activated T cells triggers a positive signal that enhances several cellular and effector functions, essential to the elimination of tumour cells.

Neil Brewis, CSO of F-star said "It is only recently that the full complexity of tumour heterogeneity and how this translates into the clinical setting has been appreciated. With the increase in tumour resistance to checkpoint therapies, there is an urgent need to generate new and efficacious treatment options for cancer patients. F-star’s new programmes have the potential to leverage a more targeted, potent and safer immune response, even in highly immune-suppressive tumour microenvironments."

The data to be presented will highlight the potent anti-tumour activity of F-star’s mAb² and how each of them outperforms combinations of monospecific agents in multiple syngeneic tumour models. Furthermore, the results will describe how F-star’s bispecific format can alleviate some of the inherent limitations of an antibody-mediated TNFRSF activation, such as low efficacy or dose-dependent liver toxicity observed in current clinical trials.

Eliot Forster, CEO of F-star said "I am very excited about the presentation of these wholly owned molecules to these conferences. The data on FS120 a dual agonist mAb² and FS222 an agonist/antagonist mAb² demonstrate the versatility and power of our Modular Antibody Technology and its ability to address the known heterogeneity of tumour types and, especially, their immune evasion mechanisms. With the potential to go beyond combination approaches, the two programmes are heading towards INDs in 2019, reinforcing F-star’s commitment to deliver life-changing treatments for cancer patients".

Details of the presentations are below:

SITC Annual Meeting – 7-11 Nov 2018 – Washington DC

Oral presentation information:

Title: FS120 mAb², a dual agonist bispecific antibody targeting OX40 and CD137, activates T cells in vitro and induces potent, FcγR-independent anti-tumour activity
Session: Next Generation Bispecifics and Antibody-Like Molecules
Session date and time: 11 Nov from 08:05-10:30

Poster presentations information:

Title: FS120 mAb², a dual agonist bispecific antibody targeting OX40 and CD137, activates T cells in vitro and induces potent, FcγR-independent anti-tumour activity
Abstract poster number: O44
Poster hall location: Hall E
Poster hall hours: 09 Nov from 08:00 – 20:00 and 10 Nov from 08:00 – 20:30
Poster presentation hours: 10 Nov from 12:20 – 13:50 and 19:00 – 20:30

Title: A novel CD137/PD-L1 bispecific antibody modulates the tumour microenvironment by activating CD8+ T cells and results in tumour growth inhibition
Abstract poster number: P631
Poster hall location: Hall E
Poster hall hours: 09 Nov from 08:00 – 20:00 and 10 Nov from 08:00 – 20:30
Poster presentation hours: 09 Nov from 12:45 – 14:15 and 18:30 – 20:00

PEGS Summit Europe 2018 – 12-16 Nov 2018 – Lisbon

Oral presentation information:

Title: Agonist bispecific antibodies delivering the next Immuno-Oncology breakthrough Session: Advancing Bispecifics and Combination Therapy to the Clinic
Presentation time: 15 Nov at 11:15

ESMO Immuno-Oncology Congress – 13-16 Dec 2018 – Geneva

Poster presentation information:

Title: Optimising TNFRSF Agonism and Checkpoint Blockade with a Novel CD137/PD-L1 Bispecific Antibody
Abstract: 444
Session date and time: 14-15 Dec, lunch time

Syros Reports Third Quarter 2018 Financial Results and Highlights Key Accomplishments and Upcoming Milestones

On November 1, 2018 Syros Pharmaceuticals (NASDAQ: SYRS), a leader in the development of medicines that control the expression of genes, reported financial results for the quarter ended September 30, 2018 and provided an update on recent accomplishments and upcoming events (Press release, Syros Pharmaceuticals, NOV 1, 2018, View Source [SID1234530647]).

"Syros continued to make great progress in the third quarter, marked by the achievement of two key 2018 goals: advancing SY-1365 into the expansion portion of the Phase 1 trial to evaluate it in multiple ovarian and breast cancer patient populations; and naming SY-5609, an oral selective CDK7 inhibitor, as our next development candidate," said Nancy Simonian, M.D., Chief Executive Officer of Syros. "Together, these accomplishments speak to our leadership in gene control, as well as our belief in the transformative potential of selective CDK7 inhibition for treating a range of solid tumors and blood cancers. Looking ahead, we expect to build on our momentum as we unveil the first-ever clinical data on a selective CDK7 inhibitor from the dose escalation portion of our Phase 1 trial of SY-1365 and present initial clinical data from the combination arms of our Phase 2 trial of SY-1425."

Upcoming Milestones:

Syros plans to present initial clinical data from cohorts in its Phase 2 trial evaluating the safety and efficacy of SY-1425 in combination with azacitidine in RARA and IRF8 biomarker-positive patients with newly diagnosed acute myeloid leukemia (AML) who are not suitable candidates for standard chemotherapy, and in combination with daratumumab in biomarker-positive patients with relapsed or refractory AML and higher-risk myelodysplastic syndrome (MDS), at the 2018 American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.
Syros plans to present clinical data from the dose escalation portion of its Phase 1 trial of SY-1365 in patients with advanced solid tumors in an oral plenary session at the 30th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Molecular Targets and Cancer Therapeutics Symposium on Thursday, November 15, 2018. The presentation will include data on safety, pharmacokinetics, and proof-of-mechanism using pharmacodynamic markers. In three additional presentations at EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper), Syros plans to present new preclinical data showing the mechanistic rationale for the ongoing clinical evaluation of SY-1365 in combination with carboplatin in ovarian cancer; the first preclinical data from its oral CDK7 inhibitor program; and the discovery of drug targets and patient subsets from its analysis of the super-enhancer landscape in ovarian cancer.
Recent Pipeline Highlights:

In October 2018, Syros selected SY-5609 as its next development candidate from a suite of internally developed, highly selective and potent oral CDK7 inhibitors. Syros is advancing SY-5609 into IND-enabling studies in oncology.
In October 2018, Syros published preclinical data supporting its hypomethylating agent (HMA) combination development strategy for SY-1425 in Haematologica, a peer-reviewed journal of the European Hematology Association (EHA) (Free EHA Whitepaper). The publication reviews data demonstrating the mechanistic rationale of SY-1425 in combination with HMAs in in vitro and in vivo models of AML with high RARA expression. SY-1425 in combination with HMAs, including azacitidine, resulted in synergistic anti-proliferative effects supported by evidence of DNA damage and apoptosis. In patient-derived xenograft models of AML with high RARA expression, SY-1425 in combination with azacitidine showed both greater clearance of tumor cells in bone marrow and other tissues and greater duration of response, compared to either azacitidine or SY-1425 alone.
In September 2018, Syros advanced SY-1365 into the expansion portion of its Phase 1 trial, opening of cohorts in ovarian and breast cancer patient populations. Based on preclinical data, showing robust anti-tumor activity in ovarian and breast cancers, a strong mechanistic rationale, and high unmet need, Syros decided to focus the initial expansion of its Phase 1 trial on these tumor types. The expansion cohorts are evaluating the safety and anti-tumor activity of SY-1365 as a single agent in primary platinum-refractory ovarian cancer patients; as a single agent in ovarian cancer patients who have relapsed after three or more therapies; in combination with carboplatin in ovarian cancer patients who have relapsed after one or more prior therapies; and in combination with fulvestrant in patients with hormone-receptor positive (HR+) metastatic breast cancer who have progressed after treatment with a CDK4/6 inhibitor. An additional cohort is enrolling patients with any solid tumor accessible for biopsy to further evaluate the mechanism of action of SY-1365.
Third Quarter 2018 Financial Results

Cash, cash equivalents and marketable securities as of September 30, 2018 were $113.2 million, compared with $72.0 million on December 31, 2017.

For the third quarter 2018, Syros reported a net loss of $15.7 million, or $0.47 per share, compared to a net loss of $13.8 million, or $0.53 per share, for the same period in 2017.

Revenues were $0.4 million for the third quarter of 2018, which relate entirely to Syros’ target discovery collaboration with Incyte Corporation. Syros did not record revenues in the third quarter of 2017.
Research and development expenses were $12.9 million for the third quarter of 2018, as compared to $10.4 million for the same period in 2017. This increase was primarily attributable to an increase in SY-1365 contract manufacturing costs and professional consulting fees in support of our clinical trials, as well as an increase in employee-related expenses.
General and administrative expenses were $3.9 million for the third quarter of 2018, as compared to $3.6 million for the same period in 2017. This increase was primarily due to an increase in employee-related expenses.
Financial Guidance

Based on its current plans, Syros believes that its existing cash, cash equivalents and marketable securities will be sufficient to fund its planned operating expenses and capital expenditure requirements into 2020.

Conference Call and Webcast:

Syros will host a conference call today at 7:30 a.m. ET to discuss these third quarter 2018 financial results and provide a corporate update.

The live call may be accessed by dialing (866) 595-4538 for domestic callers or (636) 812-6496 for international callers and referencing conference ID number: 3988733. A live webcast of the conference call will be available online on the Investors & Media section of the Syros website at www.syros.com. An archived replay of the webcast will be available for approximately 90 days.

argenx announces new cusatuzumab (ARGX-110) AML data in abstracts published in connection with 60th American Society of Hematology Annual Meeting and Exposition

On November 1, 2018 argenx (Euronext & Nasdaq: ARGX), a clinical-stage biotechnology company developing a deep pipeline of differentiated antibody-based therapies for the treatment of severe autoimmune diseases and cancer, reported updated data from the ongoing Phase 1 dose-escalation part of its Phase 1/2 clinical trial of cusatuzumab (ARGX-110) in acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) (Press release, argenx, NOV 1, 2018, View Source [SID1234530646]). As of the data cut-off on July 16, 2018, a 92% (11/12 patients) overall response rate (ORR) was observed, with 42% of patients achieving minimal residual disease (MRD) negativity. The median response duration was 6.9 months as of the data cut-off date.

Data from this ongoing AML trial are expected to be further updated, including ORR and duration of response, during a company workshop to be held around the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting.

"The clinical data published today are encouraging and underscore our decision to move forward into a Phase 2 clinical trial of cusatuzumab in AML, which we launched earlier this year. These data also support the deep understanding of the disease biology of CD70 as demonstrated by the preclinical work of our collaborators at the University of Bern, highlighting cusatuzumab’s potential to offer a novel mechanism of action in AML against leukemic blasts and leukemic stem cell compartments," commented Nicolas Leupin, MD, Chief Medical Officer of argenx. "We look forward to providing an update on key metrics from the Phase 1 dose-escalation of the Phase 1/2 trial, including response rate and duration of response, at our annual workshop around ASH (Free ASH Whitepaper)."

Phase 1/2 Results for Cusatuzumab in AML

In this trial, argenx evaluated the safety, tolerability and efficacy of cusatuzumab in combination with azacytidine (AZA) in an open-label, Phase 1/2 clinical trial in 12 newly diagnosed AML patients unfit for intensive chemotherapy. The data published today are from all 12 patients across four dose cohorts (1 mg/kg, 3 mg/kg, 10 mg/kg and 20 mg/kg) from the Phase 1/2 dose-escalation trial.

As of the data cut-off on July 16, 2018, the ORR across the 12 patients was 92% (11/12 patients), including 9 patients (82%) with a complete response with or without hematologic recovery (CR/CRi), 1 patient (9%) who reached morphologic leukemia-free status, and 1 (9%) partial response (PR). The median duration on study as of data cut-off was 6.9 months, ranging from 2 to 14.4 months, with 7 patients still on study. Five patients (42%) achieved MRD negativity as measured by flow cytometry. Translational data demonstrated that cusatuzumab monotherapy and in combination with AZA

significantly reduced leukemic stem cells in the bone marrow of AML patients. Cusatuzumab continued to be well-tolerated in AML patients across the different doses. More details can be found here.

Cusatuzumab in Cutaneous T-cell Lymphoma

argenx also announced today updated results from its non-randomized, open-label, multicenter Phase 1/2 trial of cusatuzumab in 27 patients with cutaneous T-cell lymphoma (CTCL). More details can be found here.

argenx announced in May 2018 that it is no longer devoting resources to the development of cusatuzumab in CTCL in order to focus on the drug candidate’s potential in AML.

About Cusatuzumab

Cusatuzumab (ARGX-110) is an investigational SIMPLE Antibody targeting CD70, an immune checkpoint target involved in hematological malignancies, several solid tumors and severe autoimmune diseases. Cusatuzumab is designed to: block CD70, kill cancer cells expressing CD70 through complement dependent cytotoxicity, enhanced antibody-dependent cell-mediated phagocytosis and enhanced antibody-dependent cell-mediated cytotoxicity, and restore immune surveillance against solid tumors (Silence K. et al. mAbs 2014; 6 (2):523-532). Cusatuzumab is currently being evaluated in patients with hematological malignancies, including a Phase 1/2 trial in combination with azacitidine in patients with newly diagnosed acute myeloid leukemia (AML) and high-risk myelodysplastic syndromes (MDS) and the Phase 2 part of a Phase 1/2 trial in patients with relapsed/refractory cutaneous T-cell lymphoma (CTCL). Preclinical work on cusatuzumab in AML was performed in collaboration with the Tumor Immunology Lab of Prof. A. F. Ochsenbein at the University of Bern, who won, together with Prof. Manz at the University Hospital of Zürich, the prestigious 2016 Otto Naegeli Prize for his breakthrough research on CD70/CD27 signaling with therapeutic potential for cancer patients.